American Journal for Young Scientists ยท ISSN 3068-9015
Endocrine Adaptation in Addiction: HPA Axis Plasticity as a Target for Treatment
Authors: Ananya Krishnan
Published: January 14, 2026
Category: Computational Neuroscience
Abstract
Addictive drugs often feel pleasurable at first, but over time the body develops tolerance and withdrawal symptoms through built-in ``anti-reward'' systems called opponent processes. These systems play a key role in addiction, yet their biological basis is not fully understood. Here, we propose that one such opponent process involves the body's stress hormone system, known as the hypothalamic-pituitary-adrenal (HPA) axis. We focus on alcohol addiction, where the HPA axis releases $\beta$-endorphin, which produces feelings of pleasure and pain relief. Using a mathematical model, we show that slow changes in the size and function of the HPA glands act as an internal balancing mechanism that reduces $\beta$-endorphin secretion over time. This mechanism works through fold-change detection (FCD), meaning the body responds to relative changes in hormone levels rather than absolute ones. While this process can make the system more vulnerable to addiction, it may also play an adaptive role in learning and adjustment. Our model highlights changes in gland size as potential new targets for addiction treatment.